Thymidine nucleosides

Zidovudine is an antiretroviral drug that is clinically active against HIV-1 and is intended to treat HIV-infected patients. Zidovudine is an analog of thymidine that inhibits replication of the AIDS virus. It also turned into mono-, di-, and triphosphates by the same cellular enzymes that catalyze phosphorylation of thymidine and thymidine nucleosides. Zidovudine-triphosphate is then included in the terminal fragment of the growing chain of viral DNA by viral reverse transcriptase, thus causing the viral DNA chain to break apart in cells infected with the virus. 

Pharmacology Stavudine is a synthetic thymidine nucleoside analog active against HIV. It inhibits the replication of HIV in human cells in vitro. 

It was found that when 5 -0-(4,4 -dimethoxytrityl) uridine or thymidine derivatives reacted with (n-Bu4N)2S208 in CH3CN under mild conditions, the corresponding depro-tected uridine or thymidine nucleosides were obtained in excellent yields (equation 32)"". 

Stavudine (d4T, Zerit) is a thymidine nucleoside analogue that is active against HIV-1 and HIV-2. It is approved for the therapy of HIV infection as part of a multidrug regimen and is also used for postexposure prophylaxis. 

It is synthetic thymidine nucleoside analogue, active against HIV. 

Telbivudine is a thymidine nucleoside analog with activity against HBV DNA polymerase. It is phosphorylated by cellular kinases to the active triphosphate form, which has an intracellular half-life of 14 hours. The phosphorylated compound competitively inhibits HBV DNA polymerase, resulting in incorporation into viral DNA and chain termination. It is not active in vitro against HIV-1. 

Until recently the lactol ring structure of 2-desoxy-D-ribose in nucleic acid had been proved conclusively only for the thymidine nucleoside component and in this case it was furanose in form.26 Subsequently Brown and Lythgoe,27 by application of the periodate oxidation procedure to the 2 -desoxy ribosides of guanine, hypoxanthine, cytosine and thymine, afforded proof of the presence of a furanose sugar in each compound. 

Stavudine [inn, usan] (d4T Zerit ) is a synthetic thymidine nucleoside group reverse trascriptase inhibitor ANTIVIRAL AGENT, clinically used orally in anti-hiv treatment. StC 1400 fludrocortisone. 

Scheme 10-62 Tethering the radical acceptor and precursor through an ester linkage allows stereoselective radical cyclization of 3 -phenylseIeno thymidine nucleosides.

The same group have also investigated the incorporation of the radical acceptor moiety via a silyl ether tether [76b]. A phenylseleno substituent was stereospecifically incorporated into either the 2 - or 3 -position of four thymidine nucleosides, followed by incorporation of an olefinic radical acceptor into the vicinal hydroxyl group by reaction with (allyl)dimethy]silyl chloride. In all cases, only produets resulting from a 1-endo cyclization mode were isolated after treatment with Bu3SnH/AIBN. 

Telbivudine (3), a synthetic thymidine nucleoside analog, is the unmodified L-enantiomer of the naturally occurring D-thymidine. It prevents HBV DNA synthesis by acting as an HBV polymerase inhibitor. Within hepatocytes, telbivudine (3) is phosphorylated by host cell kinase to telbivudine-5 -triphosphate which, once incorporated into HBV DNA, causes DNA chain termination, thus inhibiting HBV replication. In this sense, telbivudine (3), like most nucleotide antiviral drugs, is a prodrug. Clinical trials have shown telbivudine (3) to be significantly more effective than lamivudine (2) or adefovir dipivoxil (4) and less likely to cause resistance. ... 

Satumino, C., Buonerba, M., Boatto, G., Pascale, M., Moltedo, O., Napoli, L. D., Montesarchio, D., Lancelot, J. C. Caprariis, P. D. (2005). Synthesis and preliminary biological evaluation of a new pyiidocarbazole derivative covalently linked to a thymidine nucleoside as a potential targeted antitumoralagent. I. Chem. Pharm. Bull. 51(8), 971-974. 

A number of 4 -substituted thymidine nucleosides recently have been synthesized and show unexpected potency. The 4 -azido and 4 -azidomethyl analogs were both potent and selective, however insufficient data was provided in the preliminary publications to fully assess the selectivity of the other analogs. The azido function was not an essentid requirement for activity by this series of compounds since 4 -methyl and 4 -hydroxymethyl analogs also showed activity. It is interesting to note that 4 -cyanothymidine was quite active whereas 4 -cyano-3 -deoxythymidine was not. 

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